Reactivity of carbonyl compounds

The study of the chemistry of carbonyl compounds has shown that they can act as carbon nucleophiles in the presence of acid catalysts as well as bases. The nucleophilic reactivity of carbonyl compounds in acidic solution is due to the presence of the enol tautomer. Enolization in acidic solution is catalyzed by O-protonation. Subsequent deprotonation at carbon gives the enol ... 

Three-dimensional potential energy diagrams of the type discussed in connection with the variable E2 transition state theory for elimination reactions can be used to consider structural effects on the reactivity of carbonyl compounds and the tetrahedral intermediates involved in carbonyl-group reactions. Many of these reactions involve the formation or breaking of two separate bonds. This is the case in the first stage of acetal hydrolysis, which involves both a proton transfer and breaking of a C—O bond. The overall reaction might take place in several ways. There are two mechanistic extremes ... 

SECTION 8.4. REACTIVITY OF CARBONYL COMPOUNDS TOWARD ADDITION... 

TABLE 1.1. Reactivity of carbonyl compounds and carbenium ions."... 

Mechanism. Of great importance in permitting chemist lo explain rationally the reactivity of carbonyl compounds towattl di m -methane was the elucidation of its electronic structure. It is now accepted that a diazoalkane can be represented by a set of canonical structure ( A M C ), none of which Is an adequate representation by Itself Evidence for the linear nature of diaxoalkanee has been obtained hy various types of physical measurements, including electron diffraction and infrared fipectroeoopy.u,> 1WZ... 

Without protonation of the carbonyl group, weak nucleophiles (TV,/V-dime-thylaniline and phenol) would only react slowly or not at all with the carbonyl groups. Similarly, complexation with Lewis acids can enhance the electrophilic reactivities of carbonyl compounds. This occurs by decreasing participation (using Winstein s concept) of the neighboring oxygen... 

An Example of Chemoselectivity Relative Reactivities of Carbonyl Compounds with Respect to Nucleophiles... 

The same structural features that favour or disfavour hydrate formation are important in determining the reactivity of carbonyl compounds with other nucleophiles, whether the reactions are reversible or not. Steric hindrance and more alkyl substituents make carbonyl compounds less reactive towards any nucleophile electron-withdrawing groups and small rings make them more reactive. 

Well, you saw a diagram like this in the last chapter when we were discussing kinetic and thermodynamic products (p. 329) and you can probably also apply something of what you now know about the reactivity of carbonyl compounds towards nucleophiles to work out what is happening in this reaction between a carbonyl compound and an amine. The hydroxylamine first adds to the ketone to form an unstable intermediate similar to a hemiacetal. 

Umpolung of the Reactivity of Carbonyl Compounds Through Sulphur-Containing Reagents. Grobel, B. T. Seebach, D. Synthesis 1977, 357. 

REACTIVITY OF CARBONYL COMPOUNDS WITH ORGANOMETALLICS BEARING A SELENIUM-STABILIZED CARBANION... 

Notice that the acceptor synthons have odd numbers the donor synthon has an even number donor and acceptor properties alternate along the chain as we move away from a carbonyl group. This natural reactivity of carbonyl compounds explains why we find it easy to discuss ways of making 1,3- and 1,5-difunctionaKzed compounds, because they arise from a -1- d and from 2 + d. Reagents corresponding to synthons like d or a are rarer, and therefore compounds with 1,2- or 1,4- related functional groups require special consideration retrosynthetically. 

Domingo, L. R., Andres, J. Enhancing Reactivity of Carbonyl Compounds via Hydrogen-Bond Formation. A DFT Study of the Hetero-Diels-Alder Reaction between Butadiene Derivative and Acetone in Chloroform. J. Org. Chem. 2003, 68, 8662-8668. 

The lowest excited state of simple ketones and aldehydes corresponds to excitation of an electron from the np lone pair to the 7t -MO. The transition is forbidden in compounds of C2v symmetry. The Tocal symmetry is the same in compounds such as acetaldehyde, so that n,7t transitions of ketones and aldehydes are generally weak, 20 50 m 1 cm and they are easily overlooked in absorption spectra or hidden by the red edge of stronger 71,71 absorption. The nature of the lowest excited state is, however, decisive for the photophysical properties and the photochemical reactivity of carbonyl compounds the reactivity of n,7t excited ketones is comparable to that of alkoxy radicals (see below). 

At this point we consider some general relationships concerning the reactivity of carbonyl compounds toward addition of nucleophiles. Several factors influence the overall rate of a reaction under various conditions. Among the cmcial factors are (1) structural features of the carbonyl compound (2) the role of protons or other Lewis acids in activating the carbonyl group toward nucleophilic attack (3) the reactivity of the nucleophilic species and its influence on subsequent steps and (4) the stability of the tetrahedral intermediate and the extent to which it proceeds to product rather than reverting to starting material. 

We focus first on the inherent reactivity of the carbonyl compound itself. An irreversible processes in which the addition product is stable is the most direct means of comparing the reactivity of carbonyl compounds. In these circumstances, the relative rate of reaction of different carbonyl compounds can be directly compared. One such reaction is hydride reduction. In particular, reductions by sodium borohydride in protic... 

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